AB0322 INTESTINAL DISBIOSIS IS ASSOCIATED WITH INADEQUATE RESPONSE TO MULTIPLE ANTIRHEUMATIC DRUGS IN PATIENTS WITH RHEUMATOID ARTHRITIS.
Authors: M. Morales-Águila, A. M. Cabezas-Lucena, P. Ruiz-Limon, I. Moreno-Indias, S. Manrique Arija, N. Mena-Vázquez, A. Fernandez-Nebro
Journal: Annals of the Rheumatic Diseases (2022)

Objectives To evaluate the relationship between inadequate response to multiple antirheumatic biologic or targeted synthetic drugs (IRM-b/tsDMARDs) and intestinal microbiota and other inflammatory and severity factors in patients with rheumatoid arthritis (RA). Methods Design: A case-control study nested in a prospective cohort of RA patients. Patients: Patients with RA (ACR/EULAR 2010) from a prospective baseline cohort (incident cases between 2007-2011), &gt;16 years. Controls: subjects without inflammatory disease matched by sex and age. Protocol: All subjects were evaluated in a specialized outpatient unit. Clinical, analytical and therapeutic variables were registered using a data collection protocol. Blood, urine and faeces samples were obtained from all subjects. Variables: Dependent variable: “RA patients with IRMD”, defined as failure &gt;2 different bDMARDs (biological disease-modifying antirheumatic drug) or dsDMARDs (targeted synthetic disease-modifying antirheumatic drug). Faecal microbiota (continuous var., 0-100%) was analysed using the Ion Torrent S5 next-generation sequencing platform, and the sequences obtained were processed using the QIIME2 (Quantitative Insights Into Microbial Ecology 2) software. Inflammatory activity was measured by mean DAS-28 (disease activity score-28) throughout the disease and RA severity variables included erosions, anticitrullinated peptide antibody (ACPA) titres and HAQ (health assessment questionnaire). Other variables included socio-demographic, clinical-analytical characteristics, type of treatment with bDMARDs and reason for suspension. Statistical Analysis: descriptive, bivariate using χ 2 and T-Student followed by two logistic regression model in order to identify the factors associated with both bDMARDs and IRM-b/tsDMARDs in patients with RA. Results 220 subjects, 110 RA patients and 110 controls, were included. A total of 90/110 RA patients were seropositive (81.8%) and 68/110 were erosive (61.8%). A total of 61/110 (55.5%) were treated with any bDMARD, being more frequent the anti TNF (35.5%). Ninety-three (84.5%) of RA patients took associated sDMARD. Thirteen patients (21.3%) presented IRMD. The variables independently associated with biological therapy in RA were: physical activity (OR [95% CI], 0.990 [0.989-0.999]; p=0.043), erosions (OR [95% CI], 2.450 [1.056 -4.683]; p=0.037) and Actinobacteria family (OR [95% CI], 1.182 [1.016-1.375]; p=0.030), R2= 0.283. The variables that were independently associated with IRMD in patients with RA were: ACPA (OR [95% CI], 1.005 [1.001-1.010]; p=0.039), diagnostic delay (OR[95% CI] 1.025 [1.001-1.050]; p=0.044), age (OR [95% CI], 0.933 [0.872-0.998];p=0.032), Bacterioidetes (OR [95% CI],1.080 [1.014-1.150]; p=0.016), Synergistetes (OR [95% CI], 2.277 [1.094-4.741]; p=0.028), R2=0.329. Table 1. Epidemiological, Clinical and analytical characteristics of patients and controls. Variable Patients n=110 Controls n=110 p-value Epidemiological characteristics Age, mean (IQR) 55.9 (49.3-64.4) 56.2 (48.3-65.3) 0.917 Sex, female; n (%) 88 (80.0) 88 (80.0) 1.000 Clinical and analytical characteristics Erosions, n (%) 68 (61.8) - - RF &gt;10, n (%) 90 (81.8) 0 (0.0) &lt;0.001 ACPA &gt;20, n (%) 88 (80.0) 0 (0,0) &lt;0.001 CRP (mg/dl), median (IQR) 2,9 (2.9-6.2) 2.9 (2.9-3.3) &lt;0.001 ESR (mm/h), median (IQR) 13.0 (8.0-21.0) 11.0 (6.0-16.0) 0.008 DAS28 average, mean (±SD) 3.0 (0.7) - - HAQ average, median (IQR) 0.71 (0.3-0.9) - - sDMARD, n (%) 93 (84.5) - - bDMARD, n (%) 61 (55.5) - - Anti TNF-α, n (%) 39 (35.5) - - Anti IL-6, n (%) 9 (8.2) - - Rituximab, n (%) 7 (6.4) - - Abatacept, n (%) 2 (1.8) - - JAK inhibitor, n (%) 4 (3.6) - - Multiresistance, n (%) 13 (21.3%) - - Conclusion Biological treatment in RA was associated with less physical activity, erosions and a greater presence of Actinobacteria. Bad prognosis factors such as delayed diagnosis and elevated ACPA titres were associated with multiresistance in RA patients, in addition to higher levels of Bacteriodetes and Synergistetes. Disclosure of Interests None declared